Squamous cell carcinomas of the cervix and head and neck regions are commonly treated with definitive chemoradiotherapy. It is well established that when these tumors are hypoxic, they are much less sensitive to treatments and outcomes are poor, yet there is no method in clinical practice to determine tumor oxygen levels. Of all hypoxia imaging technologies in pre-clinical development, only EPR oximetry has the potential to be used in the clinic, on a daily basis, to measure tumor oxygen levels and to ensure that each and every fraction of radiation therapy is delivered during optimal tumor oxygenation. Importantly, there are other tumor types, such as cutaneous lymphomas, where very little is known about tumor oxygen status. We have preliminary measurements indicating that these tumors can be hypoxic and tumor oxygen levels can be elevated by carbogen breathing. In project 1, we will initiate the first multi-institutional trials to measure tumor oxygen levels over time using EPR oximetry with carbon based oxygen sensors. We will evaluate baseline fluctuations in tumor oxygen levels, the response to carbogen breathing and changes over time due to tumor growth or treatment response. These studies will provide the foundation for more advanced EPR technologies that will be introduced in the later projects. Finally, we will determine if and when normal tissue becomes hypoxic during the development of post-radiation fibrosis, which is an important survivorship issue for breast and head and neck cancer patients. We propose the following specific aims to meet the objective of this project and the overall goals of the PPG: (1) To characterize pO2 values and their temporal (in minutes to weeks) fluctuations in tumors in patients with HNSCC, cervical SCC, or CTCL. (2) To determine the response and change in pO2 induced by hyperoxygenation treatments in head and neck and cervical SCC and CTCL tumors. (3) To compare pO2 values, their temporal variation, and response to hyperoxygenation with currently used hypoxia imaging methods in head and neck and cervical cancer patients. (4) To monitor pO2 dynamics in cervical, head and neck, and CTCL tumors during and following a course of radiation therapy. (5) To monitor pO2 dynamics in radiation-induced fibrosis in breast and head and neck cancer patients who have undergone radiation therapy.